Noggin

Cerebral ischemia remains the most frequent cause of death and quality-of-life impairments due to neurological deficits, and accounts for the majority of total healthcare costs. However, treatments for cerebral ischemia are limited. Over the last decade, bone marrow stromal cell (BMSC) therapy has emerged as a particularly appealing option, as it is possible to help patients even when initiated days or even weeks after the ischemic insult. BMSCs are a class of multipotent, self-renewing cells that give rise to differentiated progeny when implanted into appropriate tissues. Therapeutic effects of BMSC treatment for ischemic stroke, including sensory and motor recovery, have been reported in pre-clinical studies and clinical trials. In this article, we review the recent progress in BMSC-based therapy for ischemic stroke, focusing on the route of delivery and pre-processing of BMSCs. Selecting an optimal delivery route is of particular importance. The ideal approach, as well as the least risky, for translational applications still requires further identification. Appropriate preprocessing of BMSCs or combination therapy has the benefi t of achieving the maximum possible restoration. Further pre-clinical studies are required to determine the time-window for transplantation and the appropriate dosage of cells.

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“…Noggin, an antagonist of BMP, regulates the differentiation of stem cells into neurons [61] . The i.v.…”

Section: Bmsc-derived Neuronal Cells (Msdncs) Inducedmentioning

confidence: 99%

Bone marrow stromal cells as a therapeutic treatment for ischemic stroke

Yang

Zhu

et al. 2014

Neurosci. Bull.

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“…Noggin is a pleiotropic factor and binds to BMP-2, BMP-4, BMP-5, BMP-7, BMP-13 and BMP-14 in vitro [19]. Noggin expression is induced by Ihh (Indian hedgehog) in chondrocytes and skeletal dysplasia results from increased noggin activity [19]. Independent of its action as a BMP antagonist, noggin binds strongly to HSPGs on the surface of cultured cells [26].…”

Section: Bmp Signalling and Heparan Sulfate Interactionmentioning

confidence: 99%

Cell biology of osteochondromas: Bone morphogenic protein signalling and heparan sulphates

Cuellar

Reddi

2013

International Orthopaedics (SICOT)

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Frequent benign outgrowths from bone known as osteochondromas, exhibiting typical endochondral ossification, are reported from single to multiple lesions. Characterised by a high incidence of osteochondromas and skeletal deformities, multiple hereditary exostoses (MHE) is the most common inherited musculoskeletal condition. While factors for severity remain unknown, mutations in exostosin 1 and exostosin 2 genes, encoding glycosyltransferases involved in the biosynthesis of ubiquitously expressed heparan sulphate (HS) chains, are associated with MHE. HS-binding bone morphogenetic proteins (BMPs) are multifunctional proteins involved in the morphogenesis of bone and cartilage. HS and HS proteoglycans are involved in BMP-mediated morphogenesis by regulating their gradient formation and activity. Mutations in exostosin genes disturb HS biosynthesis, subsequently affecting its functional role in the regulation of signalling pathways. As BMPs are the primordial morphogens for bone development, we propose the hypothesis that BMP signalling may be critical in osteochondromas. For this reason, the outcomes of exostosin mutations on HS biosynthesis and interactions within osteochondromas and MHE are reviewed. Since BMPs are HS binding proteins, the interactions of HS with the BMP signalling pathway are discussed. The impact of mouse models in the quest to better understand the cell biology of osteochondromas is discussed. Several challenges and questions still remain and further investigations are needed to explore new approaches for better understanding of the pathogenesis of osteochondromas.

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“…Noggin (Nog) is a glycosylated chemokine protein, which is able to form a neutralizing complex that prevents BMPs from binding to BMPRs (Groppe et al, 2002;Krause et al, 2011). Nog action intervene as early as during gastrulation, where it antagonizes BMP-2, -4 and -7 and generates a dorsal-ventral BMP gradient which is crucial for the germ layer formation.…”

Section: Nogginmentioning

confidence: 99%

“…Nog action intervene as early as during gastrulation, where it antagonizes BMP-2, -4 and -7 and generates a dorsal-ventral BMP gradient which is crucial for the germ layer formation. Nog effects are pleiotropic during embryo development, although they are mainly explicated toward the formation of ectoderm and mesoderm derivatives (Krause et al ,2011). In fact, Nog expression is essential for proper skeletal development, as excess BMP activity in Nog-null mice results in excess cartilage and failure to initiate joint formation, along with additional severe developmental abnormalities leading to premature embryo lethality (Brunet et al, 1998;McMahon et al, 1998;Tylzanowski et al, 2006).…”

Section: Nogginmentioning

confidence: 99%